Pharmacology and General

principles

Asmaa A.H.

Outline

• General Pharmacology.

• Source of Drugs.

• How drugs act: molecular aspects.

Receptor

Enzyme

Ion channels

Transporters

• Intrinsic activity.

Pharmacology

Pharmacology is the study of drugs and its origin, chemical

structure, preparation, administration, action, metabolism

and excretion.

The study of drugs that alter functions of living organism.

A drug is a chemical applied to physiological system that

affect its function in a specific way.

Pharmacokinetic: it mean movement of drug within body it

include; absorption, distribution, metabolism, excretion.

Pharmacodynamics: it is study of drugs-their mechanism

of action, pharmacological action, adverse effects.

Source of Drugs

The different sources of drugs are:

a. Plant:

i. Alkaloids :e.g. morphine, atropine

ii. Glycosides: e.g. Digoxin

b. Animals: Insulin, heparin.

c. Minerals: Ferrous sulphate.

d. Microorganism: Penicillin.

e. Semisynthetic: Hydromorphone.

f. Synthetic: e.g. aspirin, paracetamol.

Drugs are also produced by genetic engineering (DNA

recombinant technology) e.g human insulin, Growth hormone.

How drugs act: molecular aspects

It is a special form of drug delivery system where the

pharmacologically active agent or medicament is

selectively targeted or delivered only to its site of

action. The therapeutic response of a drug depend upon

the interaction of drug molecule with cell on cell

membrane related biological events, primary drug

targets :

• Receptor.

• Enzyme.

• Carrier protein.

• Ion channel.

ReceptorAre the sensing elements in the system of chemical

communications that coordinates the function of all the

different cells in the body.

Receptors form a key part of the system of chemical

communication that all multicellular organisms use to

coordinate the activities of their cells and organs.

Types of the receptors

1-Ligand-gated ion channels (Ionotropic receptors).

2-G-Protien Coupled receptors (Metabotropic).

3-Kinase-linked receptors.

4-Nuclear receptors.

EnzymesMany drugs are targeted on enzymes, the drug molecule

is a substrate analogue that act as competitive inhibitor

of the enzyme (e.g. Captopril, acting on ACE). In other

cases the binding is irreversible and non-competitive

(e.g. Aspirin, acting on Cox). Some drugs may require

enzymatic degradation to convert them from an

inactive form (prodrug) to an active form (e.g. Enalapril

is converted by esterase to enalaprilat which its inhibit

ACE). On the other hand enzymatic conversion of the

drug metabolite to a reactive metabolite (e.g.

Paracetamol causes liver damage).

Ion channels

Ion channel are essentially gateways in the cell

membranes that selectively allow the passage of

particular ions and that are induce to open or close by a

variety of mechanism. Two important types are ligand-

gated ion channel and voltage- gated channels. When

one or more agonist are bound, since agonist binding is

needed to activate them. Voltage-gated channels are

gated by changes in the transmembrane potential rather

than by agonist binding.

Transporters

The movement of small organic molecules across cell

membranes through transport protein because permeating

molecules are often too polar (i.e insufficiently lipid-

soluble) to penetrate lipid membranes on their own. Many

such transporters are known: those responsible for transport

of ions and many organic molecules across renal tubule,

intestinal epithelium and BBB, transport of Na+ and Ca+2

out of cells, the uptake of NT precursors (such as choline)

or of NT themselves (such as amines and amino acids) by

nerve terminals and the transport of drug molecules and

their metabolite across cell membrane and epithelial

barriers.

• Agonist: Agent which activates a receptor to produce an effect similar to that of the physiologic signal molecule (e.g. Phenylpherine).

• Partial agonist: Agent which activates a receptor to produce a sub maximal effect (e.g. Buspirone).

• Inverse agonist: Agent bind on same receptor of agonist produce an effect in the opposite direction to that of the agonist (e.g. Benzodiazepine).

• Antagonist: Agent which prevents the action of an agonist on a receptor but doesn’t have any effect of its own receptor (e.g. amlodipine).

• Competitive antagonist: If both agonist and antagonist bind to the same binding site on the receptor they are said to be competitive so prevent an agonist from binding to its receptor. (e.g. Naloxone).